Clomipramine Dosing and Titration for OCD
Starting Dose and Initial Titration
Start clomipramine at 25 mg daily and gradually increase to 100 mg over the first 2 weeks, then continue titrating up to a maximum of 250 mg daily (or 200 mg in children/adolescents), with the total daily dose given at bedtime after titration to minimize daytime sedation. 1
Week 1-2: Initial Phase
- Begin with 25 mg daily, given in divided doses with meals to reduce gastrointestinal side effects 1
- Increase gradually as tolerated to approximately 100 mg during the first 2 weeks 1
- For children and adolescents, titrate to a maximum of 3 mg/kg or 100 mg (whichever is smaller) during this initial phase 1
Week 3 and Beyond: Continuation of Titration
- After the first 2 weeks, continue increasing the dose gradually over several weeks up to a maximum of 250 mg daily in adults 1
- For children and adolescents, the maximum is 3 mg/kg or 200 mg daily, whichever is smaller 1
- Once titrated, give the entire daily dose at bedtime to minimize daytime sedation 1
Maximum Dose
- Adults: 250 mg daily maximum 1
- Children and adolescents: 200 mg daily or 3 mg/kg, whichever is smaller 1
- Higher doses are associated with greater efficacy but also higher dropout rates due to adverse effects 2
Important Timing Considerations
- Allow 2-3 weeks after each dosage change to reach steady-state plasma levels due to the long elimination half-lives of clomipramine and its active metabolite desmethylclomipramine 1
- Assess efficacy after 8-12 weeks at the target dose, though some improvement may be seen within 2-4 weeks 2
- Response is most often associated with doses greater than 75 mg/day 3
Tapering Down
When discontinuing clomipramine, taper gradually rather than stopping abruptly to avoid withdrawal symptoms, though specific tapering schedules are not provided in the FDA label. 1
Practical Tapering Approach
- Given the long half-life (mean 39 hours) 4, a gradual taper over several weeks is prudent
- Consider reducing by 25-50 mg every 1-2 weeks, monitoring for withdrawal symptoms
- Slower tapers may be needed for patients on higher doses or those with longer treatment duration
Critical Safety Warnings
MAOI Interactions
- Allow at least 14 days between discontinuing an MAOI and starting clomipramine 1
- Allow at least 14 days after stopping clomipramine before starting an MAOI 1
- Do not start clomipramine in patients receiving linezolid or intravenous methylene blue due to serotonin syndrome risk 1
Monitoring Requirements
- Carefully assess adverse effects when establishing the optimal dose, as clomipramine has a less favorable side effect profile than SSRIs 2
- Monitor for seizures and elevated aminotransferase values, which are potentially serious side effects 5
- Sexual dysfunction and seizures may be more frequent with clomipramine than other tricyclics 4
Clinical Context
Clomipramine should be reserved as a second-line or third-line agent for OCD after at least one adequate SSRI trial has failed (8-12 weeks at maximum tolerated doses) 6. SSRIs are preferred first-line due to superior safety and tolerability profiles, which is critical for long-term treatment adherence 7, 2. While some meta-analyses suggest clomipramine may be more efficacious than SSRIs, head-to-head trials show equivalent efficacy, and earlier clomipramine trials enrolled less treatment-resistant patients 7, 2.